SMLR1 (small leucine-rich protein 1) is a liver and small intestine-specific protein with emerging roles in lipid metabolism and potential anticancer activity. Primary function: SMLR1 regulates hepatic VLDL (very-low-density lipoprotein) assembly and secretion by facilitating trafficking from the endoplasmic reticulum to the Cis-Golgi complex 1. Mechanism: The protein localizes to the endoplasmic reticulum and Cis-Golgi, where it promotes VLDL biogenesis independent of microsomal triglyceride transfer protein activity 1. Disease relevance: Loss of hepatic SMLR1 causes hepatic steatosis and nonalcoholic fatty liver disease (NASH), while paradoxically reducing plasma apolipoprotein B and triglycerides, thereby protecting against diet-induced hyperlipidemia and atherosclerosis 1. Additionally, SMLR1 was identified as a novel anticancer gene in a systematic screen, suggesting potential therapeutic applications in cancer treatment 2. Clinical significance: SMLR1 represents a therapeutic target for modulating hepatic lipid metabolism and VLDL secretion; however, manipulating SMLR1 involves metabolic trade-offs between cardiovascular protection and hepatic lipid accumulation 1. The protein's role in lipid metabolism aligns with bioinformatic predictions of lipid metabolism involvement 3.